Long-term memory storage is an essential process to human life. Without long-term memory, we would not be able to remember our pasts, interpret our present, or predict our future. We would have little personal identity and functioning in a world that continues to grow in complexity would be impossible. Our research goal in the Wood lab is to understand the molecular mechanisms underlying normal long-term memory processes, memories associated with drugs of abuse, and age-related memory impairments.
It has long been known that transcription is required for a learning event to be encoded into long-term memory. Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Our lab primarily works on the HAT called CBP (e.g. Barrett et al., 2011), which we found to be essential for long-term memory formation, and HDAC3 (e.g. McQuown et al., 2011), which we have demonstrated to be a critical negative regulator of long-term memory formation.
More recently, the lab has been examining the role of another major epigenetic mechanism, nucleosome remodeling, in synaptic plasticity and memory processes. In particular, we are focused on a neuron-specific nucleosome remodeling complex called nBAF. An exciting development in the field is that many of the genes encoding nBAF subunits are mutated in human intellectual disability disorders, including Autism Spectrum Disorder. The lab is working on several subunits, including BAF53b (e.g. Vogel-Ciernia et al., 2013), and their role in memory and drug-seeking behavior.
The regulation of transcription via chromatin modification and nucleosome remodeling falls under epigenetic mechanisms of regulation. One of the alluring aspects of examining epigenetic mechanisms in modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic marks in the service of activating and/or maintaining transcriptional processes, which in turn may ultimately participate in the molecular mechanisms required for neuronal changes subserving long-lasting changes in behavior. Thus, epigenetic mechanisms provide a new frontier of neuroscience to help us understand the molecular mechanisms underlying many fascinating aspects of how the brain works.
Key Research Areas:
Epigenetics, memory, drug addiction, synaptic plasticity, aging, mouse models, physiology